Endocrine Pathology Flashcards
Organs of the Endocrine System
Pituitary gland • Thyroid gland • Parathyroid gland • Adrenal gland • Pancreas
Hypothalamus
— coordinating center
- Temperature regulation
- Food intake
- Thirst and water intake
- Sleep and awake patterns
- Emotional behavior
- Memory
Hypothalamic-pituitary axis
Involves the Thyroid gland, Adrenal glands, and Gonads
CRH (hypothalamus) –> ACTH –> cortisol (cortisol negatively feedbacks on both CRH and ACTH)
- Influences growth
- Milk production
- Water balance
General Terms in Endocrine disorders
Hypo-secretion — Hormone deficiency
Hyper-secretion — Hormone excess
Tumors — benign or malignant
Major Pituitary Gland Disorders
Acromegaly,
Diabetes insipidus,
Hypopituitarism,
Pituitary tumor
Major Anterior Pituitary Hormones
ACTH (adrenal cortex) salt and water balance, BP, blood sugar levels, muscle
strength, mood, immune system, heart, lungs, blood vessels, nervous system
o TSH = thyroid metabolism
o GH =strong bones, lean muscle, protein production
o MSH = smooth firm skin (MSH)
o FSH, LH (gonadotropins) = testes and ovaries for sex characteristics and libido
o Prolactin = breast milk production
Major Posterior Pituitary Hormones
ADH (kidney) =water retention, blood pressure
Oxytocin = muscle contraction (breast)
*note that the posterior pituitary does not PRODUCE hormones but stores hormones made in the hypothalamus
List of Pituitary Hormones
TSH — Thyroid stimulating hormone (thyrotropin)
- PRL — prolactin
- ACTH — adrenocorticotropic hormone (corticotropin)
- GH — growth hormone (somatropin)
- FSH — follicle stimulating hormone
- LH — luteinizing hormone
- MSH — melanocyte stimulating hormone
Stimulatory releasing factors (hypothalamus)
- TRH — thyrotropin releasing hormone
- CRH — corticotropin releasing hormone
- GHRH —growth hormone releasing hormone
- GnRH — gonadotropin releasing hormone
Inhibitory hypothalamic influence
- PIF — prolactin inhibiting factor
- GIH — growth inhibiting factor (somatostatin)
Hyperpituitarism — tumors
- Excess
- Adenoma, hyperplasia, carcinoma of the anterior pituitary
Hypopituitarism — small injury
- Deficit
- Destructive processes, ischemic injury, surgery, radiation, inflammatory reactions and
nonfunctional adenomas
Types of Pituitary Tumors
Adenomas (most common)
Proclatinomas
Non-functional Pituitary Adenomas
tend to be larger than those that secrete hormone
- Start out slow growing and don’t have any symptoms
- But eventually become very large
- Compress everything around it
- Thus symptoms in the beginning may not be associated with a tumor!
Compresses the optic nerve –> tunnel vision, headaches, etc
Tunnel vision = bilateral (always) compression of the optic nerve, so no peripheral vision
Secreting Pituitary Adenomas
Can effect the following cells and cause these syndromes
Lactoproh > Prolactin > Galactorrhea, Amenorrhea, Infertility
Somatotroph > GH and Prolactin > Gigantism and Acromegaly
Corticotroph > ACTH > Cushing syndrome and Nelson syndrome
Thyrotroph > TSH > Hyperthyroidism
Gonadotroph > FSH, LH > Hypogonadism and Hypopituitarism
most common alterations in pituitary adenomas
G-protein mutations
- G-proteins play a critical role in signal transduction
- G-protein hyperactivity
Gigantism
Hyperpituitaryism
Adenoma appears in children BEFORE the epiphyses have closed
Increase in body size with disproportionally long arms and legs
Acromegaly
Excessive secretion of growth hormone AFTER BONESN ALREADY FORMED (adulthood)
- Excessive growth of hands, legs, soft tissues
- Protruding jaws
- Enlargement of organs
Compression from an adenoma will create different problemsin different parts of the body - Certain body parts can’t expand anymore!!
Common signs and symptoms:
- Headaches, vision changes, hypertension, heart enlargement (from greater demand),
pulmonary problems, glucose intolerance (T2D associated with it), pain in joints,
difficulty with mobility
- Main characteristics are in the extremities
- Chief complaint at dentist = “my profile is changing and my teeth are shifting/getting
more spaces”
o Teeth get more spacing because the jaw is growing
Effects of Excess Growth Hormone in the body
Gonadal dysfunction
Diabetes mellitus
Muscle weakness
Hypertension
Arthritis
Congestive heart failure
Increased risk of GI cancer
GH regulates IGF, which is primarily secreted in the liver
- This will affect different parts of the body depending
on when the problem occurred
- Specifically, it affects bone metabolism and growth
Corticotroph adenomas
Secrete ACTH
Main characteristics:
- Cushing syndrome
- Hyperpigmentation
Cushing syndrome
Excessive production of ACTH — Cushing disease
The various causes of Cushing’s syndrome:
- 1. A pituitary tumor makes ACTH, which stimulates production of cortisol by the adrenal
gland. High cortisol levels inhibit CRH secretion and ACTH secretion from normal
pituitary cells
- 2. Ectopic ACTH secretion —a non-pituitary tumor makes ACTH, which stimulates
production of cortisol by the adrenal gland. High cortisol levels inhibit CRH secretion and
ACTH secretion from normal pituitary cells
- 3. Primary adrenal disease —adrenal glands independently make too much cortisol.
High cortisol levels inhibit CRH secretion and ACTH secretion from normal pituitary cells
Key
Most common is anterior lobe pituitary adenoma
Macroadenomas and microadenomas
Functioning – associated with endocrine signs and symptoms
Non-functioning — mass effects, visual disturbances
- Slow growing and can get very big
- First symptoms will be visual disturbances and headaches
Hypopituitarism
Low secretion of hormones Diseases of the hypothalamus or of the pituitary - Destructive disorders - Tumors/mass lesions - Traumatic brain injury - Surgery or radiation - Apoplexy - Ischemic disorders and Sheehan syndrome - Cyst - Hypothalamic lesions - Inflammatory disorders and infections
Sheehan syndrome
due to ischemic necrosis
- During pregnancy gland size increases
- If obstetrical hemorrhage occurs, relative hypoxia compromises gland
- Can also occur in DIC, sickle cell, meningitis, inflammatory disorders, and sarcoidosis
o Sickle cells can obstruct blood vessels
Anterior Pituitary Hypofunction
Clinical manifestations GH deficiency — growth failure LH and FSH —amenorrhea and infertility PRL — failure of postpartum lactation TSH and ACTH — hypothyroidism and hypoadrenalism
Diabetes Insipidus
Insufficient production of Anti-diuretic hormone
- Excessive thirst and excretion of large amounts of urine
- Thirst, blurred vision, dehydration, extreme urination, fever, diarrhea, and vomiting
Etiology — Central diabetes insipidus
- Pituitary surgery, Craniopharyngioma, Post-traumatic head injury, Congenital malformations, Genetic mutations, Autoimmune disorders, Medications (phenytoin),Cerebrovascular accident (CVA, stroke)
Etiology – Nephrogenic diabetes insipidus
- Medications (long term lithium, cisplatin, propoxyphen)
- Chronic diseases — sickle cell anemia, renal sarcoidosis, poorly controlled diabetes
mellitus
Thyroid Gland
Abnormalities in the anterior pituitary or the thyroid gland itself can result in abnormal thyroid hormone production
Thyrotropin releasing hormone (from hypothalamus) >> thyroid stimulating hormone (from anterior pituitary) >> thyroid hormone (from thyroid gland, has direct effect on gland)
3 hormones —T4, T3, Calcitonin Needed for: - Growth and maturation of tissues - Cell respiration - Energy expenditure
Function of Thyroid Hormones
T4 (thyroxine) - Oxygen consumption, cholesterol degradation, GI motility, bone
turnover, mental alertness, carb metabolism
T3 (triiodothyronine) - Heart contractility/contraction rate (increased)
Calcitonin - Skeletal remodeling, absorption of calcium, resorption of bone by osteoclasts
Hyperthyroidism
Iodine-induced hyperthyroidism
Secondary — pituitary adenoma (rare)
Clinical manifestations
- Metabolic rate
o Heart will be affected: Tachycardia and palpitations as a compensatory mechanism, but this can
lead to cardiomegaly/ Prone to arrhythmias because the heart has to work more
o Heat intolerance, weight loss, etc
o Problems with sympathetic function of GI tract (Hypermotility, malabsorption, diarrhea)
- **Malabsorption also leads to low levels of vitamins, especially VB12
- **May have problems with coagulation because of lack of vitamin K
o Weight loss even if eating a lot
- Skeletal system
o Decreased bone mass, thus prone to osteoporosis
Grave’s disease
Autoimmune disease
o Thyroid overactive»_space; Excessive amount of thyroid hormones
o Auto-antibodies to the TSH-receptor, stimulating hormone synthesis and secretion, and thyroid growth
Graves Disease is the most common cause of endogenous hyperthyroidism
- Diffuse enlargement of the gland
- Exophthalmos»_space; due to accumulation of connective tissue behind the eyes
- Long continued palpitations
- Peak 20 and 40 years of age
- Autoimmune
Hyperthyroidism —thyrotoxicosis
Thyrotoxicosis
- Excess T3 and T4 in the bloodstream
- Etiology — Ectopic thyroid tissue, multinodular goiter, thyroid adenoma, subacute
thyroiditis, ingestion of thyroid hormone, pituitary disease
- Increased metabolic activity by excessive hormone secretion increases heart rate, pulse
- Congestive heart failure may occur
- Dyspnea, Reduction of vital capacity
- GI ulcers
- RBC mass is enlarged to carry additional oxygen
- Requirements for B12 and folic acid are increased
Thyrotoxic Crisis
- Untreated or incompletely treated thyrotoxicosis
- Rare complication — marked tachycardia, arrhythmia, pulmonary edema, and HF
- Precipitating factors — infection, trauma, surgical emergencies
Hypothyroidism
Slow metabolism
In utero –> Cretinism
In adults –> Myxedema
Primary disease —Failure of the thyroid gland to produce T3 and T4; Autoimmune or damage to the thyroid gland
Secondary disease —thyroid gland is normal, but pituitary gland does not secrete TSH
Tertiary disease — failure of the hypothalamus to secrete TRH
Hashimoto’s thyroiditis
Inflammation of the thyroid gland
Autoimmune disorder
Symptoms
- Fatigue
- Muscle weakness
- Weight gain
- Bradycardia
- Thick tongue
- Eyelid edema
- Goiter
Potential causes
- Genetic predisposition
- Current autoimmune disorder
- Pregnancy or postpartum trigger
- Excessive iodine intake
- Viral of bacterial infection
- Menopause
- Drugs
Myxedema
Diminished production of thyroxin
Mucoprotein and extracellular fluid is deposited in the intracellular space, especially in dermal
connective tissue edematous appearance
- Not true edema because it’s not fluid accumulation
Decreased metabolism
Extreme fatigue
Low pulse rate
Low BP
Puffy face
Non-pitting edema
*- Vs. Pitting edema usually for cardiovascular disease; Usually bilateral, lower extremity edema
Cretinism
Dwarfism
Coarse dry skin
Deficient hair and teeth
Retarded skeletal growth
Acute infectious thyroiditis
Viral or bacterial infection
Could be related to the pharynx or upper respiratory tract
Only causes transient hypothyroidism —goes away!
Thyroiditis
Painful gland Variable enlargement Inflammation and hyperthyroid are transient 2-6 weeks High serum T4 and T3 with low TSH 6-8 weeks normal function returns NSAIDS to treat
Thyroid Cancer
Papillary carcinoma (85% of cases)
- Risk increases with prior exposure to radiation
o This is why we use the thyroid collar when taking x-rays! The thyroid is very
sensitive to radiation!!!!!!!!
Follicular carcinoma (5-15% of cases)
Anaplastic (undifferentiated) carcinoma (<5% of cases)
Medullary carcinoma (5% of cases)
Papillary carcinoma
Presents as a thyroid nodule
Rapid nodular growth
Multifocal
Hoarseness or vocal cord paralysis
Ipsilateral cervical nodes
Age at diagnosis better if between 25-40
Poorer prognosis if tumors are large
Risk factors —radiation, family history of thyroid cancer
- Exposure to ionizing radiation in childhood
- 1 st degree relative with thyroid carcinoma or family history of thyroid cancer syndrome
Parathyroid hormone (PTH)
Secreted by the parathyroid glands by their chief cells; Parathyroid gland regulates calcium homeostasis
Increases the renal tubular reabsorption of calcium, conserving free calcium
Increases the conversion of vitamin D to its active di-hydroxy form in the kidneys
Increases urinary phosphate excretion, lowering serum phosphate levels
Augments GI calcium absorption
Hyperparathyroidism
Primary — Adenoma or hyperplasia
Secondary — compensatory mechanism in response to hypocalcemia
Tertiary — persistent hypersecretion of PTH (even after prolonged hypocalcemia, after renal transplant)
Primary Hyperparathyroidism
excessive production of PTH
- Clinical — Decreased bone density (because no longer have calcium balance)
Look for areas of radiolucencies on PANs as these may be incidental findings at first if the patient has no symptoms; also IAN canal is enlarged and consistency of the bone is not the same throughout
Secondary Hyperpathyroidism
- Secondary in patients with chronic renal
disease - Has the same manifestations as primary,
but the source is different! - Called renal osteodystrophy
Symptoms of Hyperparathyroidism
- PAINFUL BONES (Bone disease)
- RENAL STONES
- ABDOMINAL GROANS (GI disturbances — nausea, peptic ulcers, gallstones)
- PSYCHIC MOANS (CNS—depression, lethargy, and seizures)
- Bones, stones, groans, and moans!!!!
- Neuromuscular — weakness and fatigue
- Cardiac — aortic and mitral valve calcifications
Hypercalcemia
—part of the differential diagnosis for hyperparathyroidism; Can be associated
with…
- Solid tumors — breast/lung/renal/head and neck
- Multiple myeloma — get lytic lesions/destruction of bone, creating more circulating Ca
- Vitamin D toxicity
- Thiazide diuretics —affect the way the body absorbs and keeps Ca
- Granulomatous disease (sarcoidosis)
- Different from hyperparathyroidism because in hypercalcemia, PTH levels will be LOW or NORMAL
Hypoparathyroidism
Less common Potential causes: - Acquired — surgically induced - Autoimmune - Familial - Congenital
Tetany — hallmark
- Neuromuscular irritability
- Tingling
- Laryngospasm = problems swallowing
- Generalized seizures
Signs of Hypoparathyroidism
Trousseau’s sign:
- Sign of latent tetany
Low calcium
Hyperreflexia
Chvostek sign:
- Twitch of the nose or lips due to stimulation of the facial nerve
- Not very specific — only in 20-30% of those with hypoparathyroidism
Dental abnormalities
- During early development
- Hypoplasia, failure of eruption, defective enamel and root formation
Diabetes Mellitus
Metabolic disorders
- Common feature — hyperglycemia
- Defects in insulin secretion, insulin action, or both
Uncontrolled diabetes affects the kidneys, eyes, and heart
- Comes with co-morbidities
1 cause of end-stage renal disease
Diabetes Mellitus
Types of Diabetes
Type 1 — Beta cell destruction, absolute insulin deficiency
- Immune mediated and idiopathic
Type 2 — Insulin resistance with relative insulin deficiency/insulin secretory defect with insulin
resistance
- Might be due to peripheral resistance to insulin action and an inadequate secretory
response by the pancreatic B cells
- Usually in adults, but because of obesity, increasing prevalence in the young
Gestational —Any degree of abnormal glucose tolerance during pregnancy
Other types —Genetic defect of beta cell function or insulin action, drug-or chemical induced,
infections, primary destruction of islet of cells, hyperpituitarism or hyperthyroidism
Classifications of Type 2 Diabetes
Other Endocrinopathies: Cushing’s Syndrome, Acromegaly,
Hyperthyroidism, Phenochromocytomas, Glucagonoma,
Infections:
- CMV
- Coxsackie B
- Congenital Rubella
Drug induced - Risk factors - Dose Duration
- Glucocorticoids
- thyroid hormone
- INF
- thiazides
- pheytoin
- Many anti-pyschotic medications lead to diabetes
Because they lead to an increase in weight gain
Which is a precursor for Type 2 Diabetes
Genetic Disorders:
- Down Syndrome
- Klinefelter syndrome
- Turner syndrome
- Prade-Willi syndrome
Gestational diabetes
Leads to increased chance of T2D later in life
- Get diabetic complications during pregnancy
- Children who are exposed to high blood glucose in the womb are at higher risk of
developing T2D later in life
Diagnosis via Lab Tests as determined by American Diabetic Association (ADA) and WHO
Glycated hemoglobin HbA1c level >6.5%
Fasting plasma glucose >126 mg/dL
Random plasma glucose >200 mg/dL
Difference between Type I and Type 2 Diabetes
TYPE 1:
-Childhood, adolescence
Normal weight or rapid weight loss
-Progressive decrease in insulin levels
-Circulating islet autoantibodies
>Good way to detect T1D!
- Diabetic ketoacidosis (fruity smelling breath)
-Dysfunction in T cell selection and regulation
leading to breakdown in self-tolerance to islet antigens
Inflammatory infiltrate of T cells and macrophages
> Macrophages destroy T cells B cell depletion, atrophy
TYPE 2:
- Usually adult/childhood and adolescence
- Obese
- Increased blood insulin early/moderate or decreased insulin late
-No islet autoantibodies
-Non-ketonic hyperosmolar coma
-Insulin resistance in peripheral tissues, failure
or compensation
-Fatty acids, inflammatory mediators linked to
insulin resistance
-Amyloid deposition in islet
- As disease advances, less cells are circulating
- Fibrotic tissue replace normal tissues of the pancreas (amyloidosis)
-Mild B cell depletion
Complications of Diabetes Mellitus
Metabolic disturbances
- Cardiovascular —accelerated atherosclerosis, HTN
- Eyes — retinopathy
- Kidney — diabetic nephropathy, renal failure
- Extremities — ulceration and gangrene
- Diabetic neuropathy —numbing/tingling/dysphagia (problem swallowing)
Pathogenesis of Type 1 Diabetes
Autoimmune
- Genetic susceptibility — HLA gene cluster on chromosome 6p21; Most common
o Rubella and enterovirus may trigger this genetic susceptibility
- Environmental factors —not entirely clear, but viral infections may be associated
- Mechanism of B cell destruction —T cells secrete cytokines, IFN, TNF that injure the
cells, and CD8 kills B cells directly
We have storage, and production of glucose
Need to have proper distribution for the
body to work
- Every cell needs glucose!
- Autoantibodies against islet
Signs and symptoms when 80-90% of the beta cells destroyed
Unable to use glucose in the peripheral tissues (needed for muscle and adipose tissue)
This stimulates secretion of counter regulatory hormones — glucagon, epinephrine, cortisol,
and growth hormone) - Get epinephrine because we’re under stress now
Patient presentation —hyperglycemia and metabolic acidosis - Buffer capacity of renal and respiratory systems reduces the pH, causing metabolic
acidosis
Pathogenesis for Type 2 Diabetes
Genetic factors
Environmental factors — obesity
- Most important!!!
Metabolic defects in diabetes
- Insulin resistance — decreased response or peripheral tissue
- Inadequate insulin secretion — B cell dysfunction
Failure of target tissues to respond normally to insulin
- Liver, skeletal muscle, and major tissues
Insulin resistance results
- Failure to inhibit endogenous glucose production (gluconeogenesis) in the liver high
fasting glucose levels
- Failure of glucose uptake in the skeletal muscle following a meal high post-prandial
blood glucose level
- Failure to inhibit activation of lipase in adipose tissue excessive triglyceride
breakdown excess circulating fatty acids
B cell Dysfunction
- Excess of free fatty acids —compromise cell dysfunction and attenuate insulin release
- Chronic hyperglycemia
- Abnormal insulin release
- Amyloid deposition — Long-standing disease
Obesity and Insulin Resistance
Multiple factors
Increases with BMI
Fat distribution
Increased risk of T2D with higher BMI, and depending on fat distribution
- Apple shape (abdominal fat accumulation)
o Visceral fat more associated with T2D
- Pear shape (waist/hip fat accumulation)
- This is evidence based! —high risk with type of fat accumulation and T2D risk!
Free fatty acids (FFAs) — compete with glucose for oxidation exacerbation the glucose
imbalance
Adipokines —proteins secreted by adipose tissue; Promote hyperglycemia
Inflammation — Important for pathogenesis/excess of FFAs and glucose
- Excess FFAs and glucose activation of inflammatory response
Markers of Diabetes in blood
Leukocytes (PMN) — impaired chemotaxis, phagocytosis, and microbicidal functions
- WBCs are there, but not working very well
- Can’t get to site, eat microorganisms, or kill them
Elevated systemic markers of inflammation
- Thus associated with periodontal disease
Micro and macrovascular complications
Clinical features — Type 1
Insulin anabolic hormone
POLYURIA (pee a lot)
POLYDIPSIA (extreme thirst)
POLYPHAGIA (extreme hunger)
Diabetic ketoacidosis
Mostly in TYPE 1
Severe acute complication
- Precipitating factors — lack of insulin, infections, trauma, and certain drugs
- Release of epinephrine — blocks insulin action, stimulates glucagon exacerbated
hyperglycemia (high range 250/600 mg)
o Infections, trauma, and drugs can increase demands on the body and cause
release of epinephrine
o This blocks insulin, stimulating glucagon, and exacerbating the hyperglycemia
- Thus get…
o Osmotic diuresis
o Ketone bodies —breakdown of adipose tissue
o Ketonemia and ketonuria —urinary excretion compromised by dehydration
Metabolic ketoacidosis
o Fatigue, nausea, vomiting, abdominal pain
o Fruity odor (breath, and also the skin)
o Deep labored breathing (Kussmaul breathing)
o CNS depression/COMA
- Treat with insulin!!!!
Hyperosmolar hyperosmotic syndrome (HHS)
Mostly in TYPE 2
Due to severe dehydration, osmotic diuresis
- Older diabetic patients — not enough water intake
- Hyperglycemia — 600-1200 mg/dl
Hypoglycemia —more common in those taking insulin medications
- Missed a meal
- Excess insulin administration
Complications
Long term hyperglycemia
Vascular complications
- Microvascular complications — retinopathy, neuropathy, and nephropathy
- Macrovascular —CV, cerebrovascular, and peripheral vascular disease
o Bigger vessels, thus more of a cardiovascular problem
Symptoms of Hyperglycemia vs. Hypoglycemia
- Hyperglycemia = dry mouth, increased thirst, blurred vision, weakness, headache,
frequent urination - Hypoglycemia = sleepiness, sweating, pallor, lack of coordination, irritability, hunger
Pancreatic Changes in Diabetes
Reduction in the number and size of cells
Leukocyte infiltration —T lymphocytes (Type 1)
Amyloid deposition/fibrosis
Increase in the number and size of islets — non-diabetic newborns/maternal hyperglycemia
Macrovascular Disease and Diabetes
Endothelial dysfunction
Atherosclerosis and cardiovascular morbidities
- Plaque/atheroma formation
o Accumulation of things the body doesn’t need —cholesterol!
o Includes inflammatory cells, dead cells, etc
Myocardial infarction —#1 morbidity seen
Gangrene of the lower extremities — in advanced vascular disease
Micro-vascular disease and Diabetes
capillary dysfunction in target organs
- Retinopathy, nephropathy, and neuropathy
Nephropathy
Kidneys are prime targets
Renal failure is second only to MI as cause of death
3 lesions are encountered in kidney
1. Glomerular lesions — nodular glomerulosclerosis as Kimmelstiel-Wilson lesion
o Capillary basement membrane thickening
2. Renal vascular lesions: arteriolosclerosis
3. Pyelonephritis, including necrotizing papillitis
Nephrotic syndrome — proteinuria (high elimination of protein), hypoalbuminemia, and edema
Poor wound Healing and Diabetes
Extrinsic and intrinsic factors
Intrinsic factors
- Hyperglycemia — Interference with collagen synthesis; Also get problem with advanced
end products/inflammation
- Changes in cellular morphology, abnormal differentiation of keratocytes
- Alteration in cytokines and growth factors
For an extraction, biggest concerns:
- Possibility of infection
- Poor wound healing
DIABETICS DO NOT HAVE ISSUES WITH BLEEDING!!!
Control of Blood Sugar
Control of blood sugar critical in delaying progression of micro-vascular disease
Control of BP and cholesterol may be more critical than control of blood glucose in averting complications with macro-vascular disease, MI and stroke
Oral Complications and Manifestations —If Diabetes poorly controlled
- Xerostomia
- Bacterial and fungal infections
- Poor wound healing
- Periodontal disease
- Burning mouth –> more related to microvascular complications
- Altered response to infection
Insulin and Cholesterol
Insulin is REQUIRED to maintain adequate levels of lipoprotein lipase, an enzyme needed to break down bad cholesterol!!
Diabetes and Periodontal Disease
Enhanced inflammatory responses
- Due to constant inflammatory response…
o Depressed wound healing
o Small blood vessel changes
Risk factors for Gestational diabetes
4% of pregnancies = 135,000 cases/year in US
- Women older than age 25
- If pre-diabetic, or if a parent or sibling (1 st degree relative) has type 2 DM
- If GDM present in previous pregnancy
- Baby delivered weighed more than 9 pounds
- Overweight before pregnancy
- Race — Black, Hispanic, American Indian, or Asian are more likely
If mother is hyperglycemic very early in 1 st trimester, DM was present before pregnancy
- She might have been pre-diabetic or diabetic before pregnancy
- Pregnancy increases its manifestation
Which adrenal gland is more likely to develop a metastasis and why?
Right side is usually more of a problem for metastasis because of the proximity to the vena cava
Structure of Adrenal Glands
Cortex –> mineralocorticoids, glucocorticoids, androgens
o Mineralocorticoids —aldosterone, corticosterone
o Glucocorticoids —cortisol, cortison
o Androgens —estrogen, testosterone
Medulla –> catecholamines, peptides
o Catecholamines —epinephrine,norepinephrine
o Peptides —somatostatin, substance P
Aldosterone
mineralocorticoid in Cortex
o Regulates physiological levels of Na and K
Corticosterone
cortisol —glucocorticoid
o metabolism
o CV function
o immune system, important for maintaining
homeostasis during periods of physical and emotional stress
o Increases BP by
potentiating the vasoconstrictor action of catecholamines and angiotensin II on
the kidney vasculature
o Anti-inflammatory; oActivates osteoclasts and inhibits osteoblasts
Chromaffin cells
Cells in the adrenal medulla which secrete cathecholamines (Epinephrine and norepinephrine)
Adrenal disorders
Adrenocortical Hyperfunction
- Overproduction= Hyperadrenalism
Adrenocortical Hypofunction
- Underproduction = Hypoadrenalism
Clinical Manifestations of Cushing Syndrome
Truncal obesity Moon facies Buffalo hump Decrease muscle mass and proximal limbs weakness Easy bruising/poor wound healing Cutaneous striae Hypertension Heart failure Acne Osteoporosis Bone fractures Diabetes Susceptibility to infection
Primary Hyperaldosteronism
Overproduction of aldosterone — suppression of the renin-angiotensin system (RAA system works to regulate kidneys/BP, thus get…) - Hypernatremia (too much sodium) - Hypokalemia (too low potassium) - Metabolic alkalosis - Elevated BP - Muscle cramps -Muscle weakness -Decreased cardiac output
Secondary hyperaldosteronism
Activation of the renin-angiotensin system
Increased levels of plasma renin
Encountered in conditions
- Decreased renal perfusion
- Arterial hypovolemia and edema HF, cirrhosis
- Pregnancy —estrogen induced increased plasma renin
o Associated with some stages of pregnancy in some patients
Addison’s Disease
Causes
- Autoimmune, Infections (AIDS, TB), Metastatic neoplasm, Genetic, Malignancy, Hemorrhage, Sepsis, Adrenalectomy, Drugs
Adrenal gland produces insufficient steroid hormones —primary insufficiency
Manifestations - Low BP - Hyperpigmentation of the skin and orally - Muscle weakness, weight loss - Headache, sweating Irritability, depression - Hypoglycemia - Muscle and joint pains - Salt craving - hyponatremia decrease aldosterone production
Adrenal crisis is a more severe state of disease
- Really creates a problem with renal system shutting down
Pheochromocytoma
—a tumor of the adrenal medulla (usually originates in chromaffin cells)
- Release catecholamines
(dopa, epi, nor-epi)
- Clinical manifestation – HTN
o Really high spike! Hypertensive emergency!
- Abrupt episodes
- Tachycardia, palpitations, headache, sweating and tremors
- Precipitated by emotional stress, exercise
- May precipitate HF, MI, arrhtytmia
Adrenocortical Neoplasms
Adenomas
Carcinomas — large invasive –> adrenal veins/vena cava
- Functional or non-functional
- Most are functional
Pancreatic Tumors
Insulinoma —Hypoglycemia
Glucagonomas — mild diabetes
Pancreatic cancer —poor prognosis, few treatment options
- Peak incidence 65/75 years
- Smoking strong risk factor
- 65% in head of the pancreas —close to the liver
- Lymph node metastases 40/75%
Signs of Pancreatic Cancer
Jaundice — biliary obstruction
o Non-specific upper abdominal pain
o Weight loss/anorexia — not in early stages
- Treatment
o Surgical resection/chemo and radiation
o Limited survival rate —thus early detection is very important
Multiple Endocrine Neoplasia (MEN) syndromes
Inherited diseases — get proliferative lesions
Hyperplasia/Adenoma/Carcinoma of multiple endocrine organs
Tumors multifocal
- In one organ, but multifocal
Can get a combination of many
MEN- 1 Wermer Syndrome
Get hyperplasia, etc in these organs:
- Parathyroid, Pancreas, Pituitay, Duodenum (gastrinomas)
Zollinger-Ellison Syndrome
- Etiology unknown
- Gastrinomas — duodenum, pancreas
- Peptic ulcers
- Insulinomas
- 55% - 90% of gastrinomas are malignant and metastasize to the lymph nodes and liver
- Genetic form —related to patients with MEN type 1
- Marked hypersecretion of gastrin origin in gastrin-producing tumors (gastrinomas)
- Arise in duodenum and peri-pancreatic soft tissues as well as pancreas (so-called gastrinoma triangle)
- Zollinger and Ellison first called attention to association of pancreatic islet cell lesions,
hypersecretion of gastric acid, and severe peptic ulceration that was present in 90-95% of patients
Multiple Endocrine Neoplasia 2
Pheochromocytoma
Thyroid and parathyroid hyperplasia
Pathogenesis of Grave’s Disease
Fibroblasts are stimulated ( retro-orbital and
dermal Fssues)
• Increased orbital soft tissue and extra-ocular
volume
• Inflammatory cells: Lymphocytes, mast cells
and macrophages. Potential impaired venous
return, pressure in optic nerve and corneal
exposure and ulcers
Presentation and Testing for Central Hypothyroidism
Central Hypothyroidism - ant. pituitary or hypothalamic hypofunction; no TSH = no T4
serum free T4-low
serum TSH-low
TSH is low and thus T4 will also be low bc nothing to stimulate the gland.
Also mRI
pituitary adenoma
prolactin might be elevated
galactorrhea = lactacting but not pregnant amenorrhea = no period Cold intolerance Fatigability Periorbital edema Bradychardia
Diseases Associated with Macroglossia
Hypothyroidism Acromegaly Mixedema Amyloidosis Angioedema
Primary hypothyroidism-
no symptoms and
signs or hypopituitarism (headaches-visual
changes or hormone excess)
Low T4
High TSH
Depression and fibromyalgia- thyroid hormone levels are normal
TXT: hormone replacement with Levothyroxine
associate with pernicious anemia due to effects of production of WBCs and RBCs however pernicious anemia is MACROCYTIC
Drugs that effect endocrine
Amiodarone (iodine) interferes with hormone
synthesis- Antiarrhythmic medication
• Lithium- Psychiatric medication-interferes
with secretion
Symptoms of Phenochromcytoma
Headaches Diaphoresis Palpitations Paroxymal HTN (explosive high BP) Symptoms progress was tumor grows
EXCESS OF CATECOLAMINES (epi and nor-epi)
Sheenhan Syndrome Symptoms
Cold intolerance - thyroid hormone deficiency
Weight gain - thyroid hormone deficiency
Fatigue and weakness - adrenal gland
Hot flashes/amenorrhea - Gonadotropin deficiency
IE VASCULAR HYPOPITITUARISM
TXT: hormone replacement
Brittle nails (nail dystrophy) can be seen in…
Hypoparathyroidism
due to hypocalcemia
